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IL12/23 Blockade with Ustekinumab as a Treatment for Immune-Related Cutaneous Adverse Events

Background: Immune-related cutaneous adverse events (ircAEs) are frequent and may reduce quality of life and consistent dosing. IL12/23 has been implicated in psoriasis, which is reminiscent of the psoriasiform/lichenoid ircAE phenotype. We report the use of ustekinumab as a therapeutic option. Meth...

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Autores principales: Gu, Stephanie L., Maier, Tara, Moy, Andrea P., Dusza, Stephen, Faleck, David M., Shah, Neil J., Lacouture, Mario E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10674871/
https://www.ncbi.nlm.nih.gov/pubmed/38004414
http://dx.doi.org/10.3390/ph16111548
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author Gu, Stephanie L.
Maier, Tara
Moy, Andrea P.
Dusza, Stephen
Faleck, David M.
Shah, Neil J.
Lacouture, Mario E.
author_facet Gu, Stephanie L.
Maier, Tara
Moy, Andrea P.
Dusza, Stephen
Faleck, David M.
Shah, Neil J.
Lacouture, Mario E.
author_sort Gu, Stephanie L.
collection PubMed
description Background: Immune-related cutaneous adverse events (ircAEs) are frequent and may reduce quality of life and consistent dosing. IL12/23 has been implicated in psoriasis, which is reminiscent of the psoriasiform/lichenoid ircAE phenotype. We report the use of ustekinumab as a therapeutic option. Methods: Patients at Memorial Sloan Kettering Cancer Center, New York, who received immune checkpoint inhibitors and were treated with ustekinumab or had the keywords “ustekinumab” or “Stelara” in their clinical notes between 1 March 2017 and 1 December 2022 were retrospectively identified via a database query. Documentation from initial and follow-up visits was manually reviewed, and response to ustekinumab was categorized into complete cutaneous response (CcR, decrease to CTCAE grade 0), partial cutaneous response (PcR, any decrease in CTCAE grade exclusive of decrease to grade 0), and no cutaneous response (NcR, no change in CTCAE grade or worsening). Labs including complete blood count (CBC), cytokine panels, and IgE were obtained in a subset of patients as standard of care. Skin biopsies were reviewed by a dermatopathologist. Results: Fourteen patients with psoriasiform (85.7%), maculopapular (7.1%), and pyoderma gangrenosum (7.1%) ircAEs were identified. Ten (71.4%) receiving ustekinumab had a positive response to treatment. Among these 10 responders, 4 (40%) demonstrated partial cutaneous response and 6 (60%) demonstrated complete cutaneous resolution. Six patients (42.9%) experienced interruptions to their checkpoint inhibitor treatment as a result of intolerable ircAEs, and following ircAE management with ustekinumab, two (33.3%) were successfully rechallenged with their checkpoint inhibitors. On histopathology, patients primarily had findings of interface or psoriasiform dermatitis. No patients reported an adverse event related to ustekinumab. Conclusions: Ustekinumab showed a benefit in a subset of patients with psoriasiform/lichenoid ircAEs. No safety signals were identified. However, further prospective randomized controlled trials are needed to confirm our findings.
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spelling pubmed-106748712023-11-02 IL12/23 Blockade with Ustekinumab as a Treatment for Immune-Related Cutaneous Adverse Events Gu, Stephanie L. Maier, Tara Moy, Andrea P. Dusza, Stephen Faleck, David M. Shah, Neil J. Lacouture, Mario E. Pharmaceuticals (Basel) Brief Report Background: Immune-related cutaneous adverse events (ircAEs) are frequent and may reduce quality of life and consistent dosing. IL12/23 has been implicated in psoriasis, which is reminiscent of the psoriasiform/lichenoid ircAE phenotype. We report the use of ustekinumab as a therapeutic option. Methods: Patients at Memorial Sloan Kettering Cancer Center, New York, who received immune checkpoint inhibitors and were treated with ustekinumab or had the keywords “ustekinumab” or “Stelara” in their clinical notes between 1 March 2017 and 1 December 2022 were retrospectively identified via a database query. Documentation from initial and follow-up visits was manually reviewed, and response to ustekinumab was categorized into complete cutaneous response (CcR, decrease to CTCAE grade 0), partial cutaneous response (PcR, any decrease in CTCAE grade exclusive of decrease to grade 0), and no cutaneous response (NcR, no change in CTCAE grade or worsening). Labs including complete blood count (CBC), cytokine panels, and IgE were obtained in a subset of patients as standard of care. Skin biopsies were reviewed by a dermatopathologist. Results: Fourteen patients with psoriasiform (85.7%), maculopapular (7.1%), and pyoderma gangrenosum (7.1%) ircAEs were identified. Ten (71.4%) receiving ustekinumab had a positive response to treatment. Among these 10 responders, 4 (40%) demonstrated partial cutaneous response and 6 (60%) demonstrated complete cutaneous resolution. Six patients (42.9%) experienced interruptions to their checkpoint inhibitor treatment as a result of intolerable ircAEs, and following ircAE management with ustekinumab, two (33.3%) were successfully rechallenged with their checkpoint inhibitors. On histopathology, patients primarily had findings of interface or psoriasiform dermatitis. No patients reported an adverse event related to ustekinumab. Conclusions: Ustekinumab showed a benefit in a subset of patients with psoriasiform/lichenoid ircAEs. No safety signals were identified. However, further prospective randomized controlled trials are needed to confirm our findings. MDPI 2023-11-02 /pmc/articles/PMC10674871/ /pubmed/38004414 http://dx.doi.org/10.3390/ph16111548 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Brief Report
Gu, Stephanie L.
Maier, Tara
Moy, Andrea P.
Dusza, Stephen
Faleck, David M.
Shah, Neil J.
Lacouture, Mario E.
IL12/23 Blockade with Ustekinumab as a Treatment for Immune-Related Cutaneous Adverse Events
title IL12/23 Blockade with Ustekinumab as a Treatment for Immune-Related Cutaneous Adverse Events
title_full IL12/23 Blockade with Ustekinumab as a Treatment for Immune-Related Cutaneous Adverse Events
title_fullStr IL12/23 Blockade with Ustekinumab as a Treatment for Immune-Related Cutaneous Adverse Events
title_full_unstemmed IL12/23 Blockade with Ustekinumab as a Treatment for Immune-Related Cutaneous Adverse Events
title_short IL12/23 Blockade with Ustekinumab as a Treatment for Immune-Related Cutaneous Adverse Events
title_sort il12/23 blockade with ustekinumab as a treatment for immune-related cutaneous adverse events
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10674871/
https://www.ncbi.nlm.nih.gov/pubmed/38004414
http://dx.doi.org/10.3390/ph16111548
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